Dync1h1 mutation

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Gylnx

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I am not sure if anyone has used nebula for full exome sequencing. They put polygenic score for Parkinson’s and ALS for me at 100 percentile and incidentally I found a possible pathogenic mutation in Dync1h1 gene. I would suggest staying away from the polygenic score as it does not predict anything but I haven’t been able to find anyone to interpret the mutation. I am not sure if this is related to neuropathy that I have in leg. I attached their report in case anyone knows how to interpret it.
 

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Previous thread

Academic medical centers have genetic counselors who can help you interpret the data. Just to be correct, there is no such thing as the 100th percentile because if everyone were below you, that would include you.

How are things with your kids?
 
I talked to genetic counselor at genome medical but they are not sure how to interpret it. There seems to be KIF5A related SNPs that are mentioned in the attached article.

Thankfully no one in the family showing any symptoms other than BFS. My neurologist thought I had Parkinson’s but it was ruled out with a second opinion.
 

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DYNC1H1 was negative in invitae testing. Genetic counselor wanted to see raw data to compare to nebula. So far it seems though they may be inaccurate and the polygenic risk score they show may be non-sensical.

If anyone has else has a nebula report for these, I would like to compare and see the reason for high score. Nebula does not offer genetic counseling, and no one can interpret their reports, which is very confusing.

<links to commercial site removed>
 
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I deleted the reports bc they live on Nebula's commercial site.

As far as I am concerned, they are claptrap. The basis for your imaginary "100%" PD percentile is supposed to be 5000 other Nebula users? That is hardly scientific risk estimation. As for the mish-mosh of "positive" and "negative" effect variants listed, we don't have the hard data that would make most any of them telling, let alone in combination. And you say Parkinson's was ruled out in your case, so the point of this testing seems even more opaque.

Most neuropathy is not genetic. If you have a neuropathy, treat it as best you can and don't let yourself drown in these data [sic]. This whole area is far from ready for primetime and is essentially an ATM for startups at this point, when it comes to CNS disorders that from all we know are primarily triggered by other-than-genetic catalysts. Of course, there are genetically-mediated forms of ALS and PD. But your reports are far from that situation.

Best,
Laurie
 
I agree. What is irresponsible on their part is that they are identifying mutation as pathogenic where the mutation is actually benign, and in some cases the mutations were not identified correctly. The polygenic score is unproven and is based on small number of samples.
 
Hi, I saw a pulmonologist due to inability to inhale fully like before. MIP was 34 and MEP was 80. I had restricted pattern in PFT and have mostly right sided stiffness with cervical stenosis. I was wondering other than myopathy or neuromuscular disease that can be diagnosed, is there an alternate reason for the low MIP value such as degenerative disc diseases or something more common? The reason for asking it I am looking to preserve my lung function if possible to address the underlying condition. Currently not on any medication and I experience rib pain (heart issues ruled out) and it is very difficult to breath during common cold or flu/Covid..

I asked both the pcp and pulmonologist but they are not sure. Should I discuss this with a neuromuscular specialist or rheumatologist?

CT showed the following
1. Diffuse bronchial wall thickening without evidence for pneumonia or
pulmonary fibrosis.
2. Scattered calcified granulomata.
 
Hi there-

I've moved your post to your already open thread. It help keep things tidy and allows people to see what questions have been asked and answered already, all in one place. Mind, this question does not involve ALS in any way shape or form and this forum is focused on that. It might be a better idea to go on a more general health forum or one focused on breathing issues to ask your questions.
 
The good news is that with ALS the MEP is likely to be far lower, and the problem is not restrictions. PALS have more difficulty expelling air, than breathing in enough.

We really can't answer things your doctor can't as we just have some text descriptions by you. Your doctor is seeing you and doing the examinations and tests. All the best.
 
Even though ALS presents in a restrictive pattern, there are many other reasons for lower lung capacity. Even things like bruised ribs can reduce MIP and present as a restrictive pattern in PFT.

If your current pulmonologist is stumped, get a second opinion.
 
Thanks for this information. I set up a new appt with pulmonologist.
 
Just for update, local ALS clinic was able to help with this and ordered supine spirometry since MIP is very low and may indicate diaphragm weakness due to another type of neuromuscular issue.
 
The new Pulmonary rehab specialist is also a neurologist and he is prescribing NVS as cpap or bipap is not suitable for respiratory muscle weakness. I am glad that I looked for a second opinion as the breathlessness was becoming difficult to recover from every morning.
 
It turned out invitae uses an older genome model hg37 and nebula uses hg38, leading to discrepancies. I have requested the variant list for appointment with neurology as the MIP 40 and MEP 80 cutoff points do indicate neuromuscular weakness according to the new pulmonologist at MDA clinic. The previous pulmonary Dr did not have neuromuscular specialty.
 
Based on the genetic testing and drop in FVC in supine position, I was diagnosed with diaphragm weakness due to hereditary motor neuron disease (likely SMA-4) . The Dr. ordered non invasive ventilator to be used at night but assured that this will not decline fast and pulmonary symptoms will likely get better with NVS therapy.
 
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